학술논문

Clinical Utility of Liquid Biopsy to Detect BRAF and NRAS Mutations in Stage III/IV Melanoma Patients by Using Real-Time PCR.
Document Type
Article
Source
Cancers. Jul2022, Vol. 14 Issue 13, pN.PAG-N.PAG. 14p.
Subject
*DNA analysis
*REVERSE transcriptase polymerase chain reaction
*GENETIC mutation
*MELANOMA
*HEALTH outcome assessment
*INDIVIDUALIZED medicine
*TUMOR classification
*CANCER patients
*IMMUNOTHERAPY
BODY fluid examination
Language
ISSN
2072-6694
Abstract
Simple Summary: Liquid biopsy is an increasingly used tool for melanoma diagnosis and molecular characterization, but also for monitoring of response to anticancer drugs. The aim of our work is to assess the clinical utility of a real-time quantitative PCR (qPCR)-based platform with a very short turnaround time and identify the best setting for clinical investigation. We investigated the concordance of this technique with tissue analysis in stage III–IV melanoma patients; moreover, we correlated results to clinicopathologic characteristics and outcomes. We found a higher tissue–plasma concordance in melanoma patients with high burden of disease (sum of diameters ≥30 mm, ≥2 metastatic sites, elevated LDH levels), constituting a clinical subgroup worthy of future prospective evaluation; however, the low sensitivity of this technique seems to be not sufficient for predicting relapses in radically resected patients. Background: Liquid biopsy is a potentially useful tool for melanoma patients, also for detecting BRAS/NRAS mutations, even if the tissue analysis remains the current standard. Methods: In this work, we tested ctDNA on plasma samples from 56 BRAF-V600/NRAS mutant stage III/IV melanoma patients using a real-time quantitative PCR (qPCR)-based platform. The study population was divided into two cohorts: the first including 26 patients who had undergone radical resection (resected cohort) and the second including 30 patients who had unresected measurable disease (advanced cohort). Moreover, for 10 patients in the advanced cohort, ctDNA assessment was repeated at specified timepoints after baseline testing. Data were analyzed and correlated to the clinicopathologic characteristics and outcomes. Results: In the baseline cohort, a higher tissue–plasma concordance was seen in patients with high burden of disease (sum of diameters ≥30 mm, ≥2 metastatic sites, elevated LDH levels); furthermore, monitoring of these patients through ctDNA analysis was informative for therapeutic responses. On the other hand, the low sensitivity of this technique did not allow for clinically valuable prediction of relapses in radically resected stage III/IV patients. Conclusions: Overall, our data suggest that qPCR-based ctDNA analysis could be informative in a subset of locally advanced and metastatic melanoma patients with specific clinical–radiological characteristics, supporting further investigations in this setting. [ABSTRACT FROM AUTHOR]